Disseminated Skeletal Cryptococcosis: A Case Report

Journal of Orthopaedic Case Reports · 2025-01-01 · 1 citations

Introduction: Cryptococcus is a rare cause of osteomyelitis, especially in immunocompromised individuals. This case report discusses a rare case of disseminated cryptococcosis with multiple bone lesions in a patient with isolated CD4 lymphocytopenia. Case Report: A 31-year-old apparently normal Indian male presented with pain and swelling of his right proximal femur for 8 months without any history of trauma. He also reported a similar swelling in his chest wall with allergic respiratory symptoms for 8 years. Laboratory analysis revealed mild elevation in inflammatory markers. Magnetic resonance imaging of the pelvis revealed osteolytic lesions in the right proximal femur and pubic bone with soft tissue collections, and computed tomography scan of the chest showed an osteolytic lesion in the right 9th rib with an overlying soft tissue collection and a subpleural cavitary nodule in the left lower lobe posterior basal segment. Although initially treated as a case of clinically diagnosed tuberculosis, the patient did not get any relief with antitubercular therapy. Fine needle aspiration cytology and fungal culture identified Cryptococcus neoformans from both lesions and from the blood culture. The patient responded well to antifungal treatment and is currently symptom free. Conclusion: Cryptococcosis should be considered as a rare differential diagnosis in patients presenting with bone pain and multiple lytic lesions. Definitive diagnosis requires a fungal culture from the affected areas. Early treatment with antifungals is important in preventing complications and death.

Limited Sampling Strategy of Rosuvastatin Single-Time-point Concentrations Accurately Estimate Exposure and Constitutive Transporter Activities in Healthy Adults

Therapeutic Drug Monitoring · 2025-10-01

BACKGROUND: Rosuvastatin is commonly used as an exogenous probe drug to evaluate the activities of organic anion-transporting polypeptide (OATP) 1B1/3 and breast cancer resistance protein (BCRP). The authors evaluated a limited sampling strategy for rosuvastatin plasma concentrations to estimate exposure and potential OATP1B1/3 and BCRP activities. METHODS: Plasma concentration versus time data were obtained from 36 healthy adults (8 women) from 2 published studies. Participants were administered a single oral dose (10 mg) of rosuvastatin under constitutive transporter conditions and concurrently with botanical goldenseal, green tea extract, or soy isoflavones. Backward stepwise linear regression generated single-time-point-limited sampling models (LSMs). Noncompartmental pharmacokinetic analysis was used to determine the area under the concentration versus time curve from time zero to the last measured concentration (AUC last ) from intensive sampling. No-effect boundary testing was performed to determine whether the LSMs reproduced the same outcome (i.e., presence or lack of interaction) as intensive sampling. RESULTS: A 4-hour and 6-hour single-time-point concentration LSM accurately estimated the AUC last under constitutive OATP1B1/3 and BCRP conditions. Both rosuvastatin LSMs detected interactions with the green tea extract. Conflicting results regarding interactions with goldenseal and soy isoflavones were observed, with changes in exposure ranging from 11% to 14%. CONCLUSIONS: Limited sampling strategy of rosuvastatin concentrations accurately estimated AUC last during constitutive OATP1B1/3 and BCRP conditions but should be used with caution during altered transporter conditions.

Comparison of Risk Prediction Models to Estimate Opioid-Induced Respiratory Depression, Oversedation, and Overdose in Patients with Cancer

Journal of Pain & Palliative Care Pharmacotherapy · 2025-03-20 · 1 citations

= 19), respectively. Additional research is needed to evaluate model calibration to increase OIRD, oversedation, and overdose prediction model validity and generalizability for future clinical implementation.

Expanding Role of Endogenous Biomarkers for Assessment of Transporter Activity in Drug Development: Current Applications and Future Horizon

Pharmaceutics · 2024-06-25 · 6 citations

The evaluation of transporter-mediated drug-drug interactions (DDIs) during drug development and post-approval contributes to benefit-risk assessment and helps formulate clinical management strategies. The use of endogenous biomarkers, which are substrates of clinically relevant uptake and efflux transporters, to assess the transporter inhibitory potential of a drug has received widespread attention. Endogenous biomarkers, such as coproporphyrin (CP) I and III, have increased mechanistic understanding of complex DDIs. Other endogenous biomarkers are under evaluation, including, but not limited to, sulfated bile acids and 4-pyridoxic acid (PDA). The role of endogenous biomarkers has expanded beyond facilitating assessment of transporter-mediated DDIs and they have also been used to understand alterations in transporter activity in the setting of organ dysfunction and various disease states. We envision that endogenous biomarker-informed approaches will not only help to formulate a prudent and informed DDI assessment strategy but also facilitate quantitative predictions of changes in drug exposures in specific populations.

Longitudinal Evaluation of the Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression in Patients with Cancer

Journal of Pain & Palliative Care Pharmacotherapy · 2024-11-22 · 2 citations

= 0.14-0.31). CIP-RIOSORD intraindividual variability was low to moderate; the median (range) coefficient of variation was 22.3% (0-173%). Beyond a baseline OIRD/overdose risk assessment, reevaluation of such risk using the CIP-RIOSORD does not to be performed at each palliative care visit.

Evaluating the Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in Patients with Cancer

Journal of Pain & Palliative Care Pharmacotherapy · 2024-04-02 · 3 citations

= 27, 35%). Based on the CIP-RIOSORD, there is a 15% probability of experiencing a serious OIRD event or overdose within the next 6 months.

Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach

Therapeutic Drug Monitoring · 2023-01-13 · 2 citations

BACKGROUND: Fexofenadine is a recommended in vivo probe drug for phenotyping P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 transporter activities. This study evaluated a limited sampling strategy using a population pharmacokinetic approach to estimate plasma fexofenadine exposure as an index of P-gp and OATP activities. METHODS: In a previous study, a single oral dose of fexofenadine (120 mg) was administered alone or in combination with grapefruit juice, Panax ginseng , or Echinacea purpurea to healthy adult participants. Serial plasma samples were collected up to 72 hours after administration and fexofenadine concentrations were measured. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Limited sampling models (LSMs) using single and 2-timepoint fexofenadine concentrations were compared with full profiles from intense sampling using empirical Bayesian post hoc estimations of systemic exposure derived from the population pharmacokinetic model. Predefined criteria for LSM selection and validation included a coefficient of determination (R 2 ) ≥ 0.90, relative percent mean prediction error ≥ -5 to ≤5%, relative percent mean absolute error ≤ 10%, and relative percent root mean square error ≤ 15%. RESULTS: Fexofenadine concentrations (n = 1520) were well described using a 2-compartment model. Grapefruit juice decreased the relative oral bioavailability of fexofenadine by 25%, whereas P. ginseng and E. purpurea had no effect. All the evaluated single timepoint fexofenadine LSMs showed unacceptable percent mean prediction error, percent mean absolute error, and/or percent root mean square error. Although adding a second time point improved precision, the predefined criteria were not met. CONCLUSIONS: Identifying novel fexofenadine LSMs to estimate P-gp and OATP1B1/3 activities in healthy adults for future transporter-mediated drug-drug interaction studies remains elusive.

Utility of endogenous 4β-hydroxycholesterol as a biomarker to assess cytochrome P 450 3A (CYP3A) activity: not quite ready for prime time

European Journal of Clinical Pharmacology · 2022-09-13 · 4 citations

an open-label, three-arm study evaluating hepatic and intestinal cytochrome P450 (CYP) 3A4 activity utilizing the 4-hydroxycholesterol concentrations as an endogenous biomarker to evaluate CYP3A4 activity in patients with a wide body weight range (n = 78, BMI 18.5 to greater than 40 kg/m 2 ) The authors are to be commended for evaluating organ-specific quantitative CYP3A4 protein expression and microsomal ex vivo activity. The subject participants are also to be commended for providing liver and small intestinal biopsies. 4-hydroxycholesterol concentrations correlated with hepatic CYP3A4 concentrations (Spearman r = 0.3, p = 0.027) and with hepatic microsomal CYP3A4 activity (Spearman r = 0.53, p < 0.001). Intestinal CYP3A4 concentrations and microsomal CYP3A4 activity did not correlate with 4-hydroxycholesterol concentrations. The authors concluded this study "provides evidence that 4-hydroxycholesterol concentrations is a suitable marker for hepatic CYP3A4 phenotyp[ing]"

Exploring the Expanded Role of Pharmacists in Advance Care Planning

JCO Oncology Practice · 2021-01-08 · 3 citations

PURPOSE: Advance care planning (ACP) is a clinical skill that can be taught. An opportunity exists to teach how to conduct ACP to clinicians not typically engaged in these conversations to increase the likelihood that patients and caregivers engage in ACP. We conducted a prospective study exploring the feasibility of a pharmacist-led ACP intervention. METHODS: We completed a prospective, single-center study from July 2015 to July 2017. We included patients of age ≥ 18 years with incurable cancer referred to the palliative care clinic. A trained pharmacist led an ACP discussion with the patient and selected proxy. We defined feasibility as completion of ≥ 30 pharmacist-led ACP discussions over the study period. Additionally, we defined an informed healthcare proxy as someone who understood three key end-of-life (EOL) treatment preferences: the patient's personal definition of quality of life, desired resuscitation status, and preferred location of death (in or out of the hospital). Patients were followed until the end of the study or death. For those patients who died, the pharmacist contacted the proxy for follow-up and explored satisfaction with the ACP intervention. RESULTS: Thirty-four patients completed the study. All selected proxies completed the intervention and were able to understand the three EOL preferences. At the time of the patient’s death (n = 20), proxies reported that 66.6% received their preferred resuscitation status and 72.2% died in their preferred location. Proxy satisfaction with the ACP process was 7.6 ± 2.5 (mean ± SD) on a 11-point Likert scale. CONCLUSION: These findings indicate the potential for pharmacists to lead and engage in ACP in the outpatient setting.

S-warfarin limited sampling strategy with a population pharmacokinetic approach to estimate exposure and cytochrome P450 (CYP) 2C9 activity in healthy adults

European Journal of Clinical Pharmacology · 2021-03-23 · 1 citations